LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and show characteristics of skeletal muscle differentiation. The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF...

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Bibliographic Details
Published in:Oncotarget 2017-01, Vol.8 (2), p.3259-3273
Main Authors: Dräger, Julia, Simon-Keller, Katja, Pukrop, Tobias, Klemm, Florian, Wilting, Jörg, Sticht, Carsten, Dittmann, Kai, Schulz, Matthias, Leuschner, Ivo, Marx, Alexander, Hahn, Heidi
Format: Article
Language:English
Subjects:
Apoptosis - genetics
Biomarkers, Tumor
Biopsy
Cell Differentiation - genetics
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation
Disease Progression
Gene Expression
Gene Knockdown Techniques
Humans
Lymphoid Enhancer-Binding Factor 1 - genetics
Lymphoid Enhancer-Binding Factor 1 - metabolism
Neoplasm Grading
Research Paper
Rhabdomyosarcoma - genetics
Rhabdomyosarcoma - metabolism
Rhabdomyosarcoma - pathology
Tissue Array Analysis
Wnt Signaling Pathway
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Summary:Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and show characteristics of skeletal muscle differentiation. The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF transcription factor LEF1 when compared to normal skeletal muscle and that LEF1 can restrain aggressiveness especially of ARMS cells. LEF1 knockdown experiments in cell lines reveal that depending on the cellular context, LEF1 can induce pro-apoptotic signals. LEF1 can also suppress proliferation, migration and invasiveness of RMS cells both in vitro and in vivo. Furthermore, LEF1 can induce myodifferentiation of the tumor cells. This may involve regulation of other LEF1/TCF factors i.e. TCF1, whereas β-catenin activity plays a subordinate role. Together these data suggest that LEF1 rather has tumor suppressive functions and attenuates aggressiveness in a subset of RMS.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.13887